Analgesic

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"Painkiller" redirects here. For other uses, see Painkiller (disambiguation).

An anaIgesic (also known as a painkiIIer) is any member of the group of drugs used to
relieve pain (achieve analgesia). The word analgesic derives from Greek an- ("without") and algos ("pain").
Analgesic drugs act in various ways on the peripheral and central nervous systems; they
include paracetamol (para-acetylaminophenol, also known in the US as acetaminophen), the non-steroidal anti-
inflammatory drugs (NSADs) such as the salicylates, and opioid drugs such as morphine andopium. They are
distinct from anesthetics, which reversibly eliminate sensation.
n choosing analgesics, the severity and response to other medication determines the choice of agent; the
WHO pain ladder, originally developed in cancer-related pain, is widely applied to find suitable drugs in a
stepwise manner.
[1]
The analgesic choice is also determined by the type of pain: forneuropathic pain, traditional
analgesics are less effective, and there is often benefit from classes of drugs that are not normally considered
analgesics, such as tricyclic antidepressants and anticonvulsants.
[2]

The major classes
!aracetamoI and NSAIDs
ain article: Non-steroidal anti-inflammatory drug
The exact mechanism of action of paracetamol/acetaminophen is uncertain, but it appears to be acting
centrally rather than peripherally (in the brain rather than in nerve endings). Aspirin and the other non-steroidal
anti-inflammatory drugs (NSADs) inhibit cyclooxygenases, leading to a decrease in prostaglandin production.
This reduces pain and also inflammation (in contrast to paracetamol and the opioids).
[citation needed]

Paracetamol has few side effects and is regarded as safe, although intake above the recommended dose can
lead to liver damage, which can be severe and life-threatening, and occasionally kidney damage. NSADs
predispose to peptic ulcers, renal failure, allergic reactions, and occasionallyhearing loss, and they can
increase the risk of hemorrhage by affecting platelet function. The use of aspirin in children under 16 suffering
from viral illness has been linked to Reye's syndrome, a rare but severe liver disorder.
[edit] inhibitors
ain article: COX-2 inhibitor
These drugs have been derived from NSADs. The cyclooxygenase enzyme inhibited by NSADs was
discovered to have at least 2 different versions: COX1 and COX2. Research suggested that most of the
adverse effects of NSADs were mediated by blocking the COX1 (constitutive) enzyme, with the analgesic
effects being mediated by the COX2 (inducible) enzyme. The COX2 inhibitors were thus developed to inhibit
only the COX2 enzyme (traditional NSADs block both versions in general). These drugs (such
as rofecoxib and celecoxib) are equally effective analgesics when compared with NSADs, but cause less
gastrointestinal hemorrhage in particular. However, post-launch data indicated increased risk of cardiac and
cerebrovascular events with these drugs; this is probably due to an imbalance in blood coagulation. Rofecoxib
(marketed as Vioxx) was subsequently withdrawn from the market. The role for the remaining members of this
class of drug is debated.
[edit]piates and morphinomimetics
ain articles: Opioid and Opiate
orphine, the archetypal opioid, and various other substances
(e.g. codeine, oxycodone, hydrocodone, dihydromorphine, pethidine) all exert a similar influence on
the cerebral opioid receptor system. Buprenorphine is thought to be a partial agonist of the opioid receptor,
and tramadol is an opiate agonist with SNR properties.
[citation needed]
Tramadol is structurally closer
to venlafaxine than to codeine and delivers analgesia by not only delivering "opiate-like" effects (through mild
agonism of the mu receptor) but also by acting as a weak but fast-acting serotonin releasing
agent andnorepinephrine reuptake inhibitor.
[3][4][5][6]
Dosing of all opioids may be limited by opioid toxicity
(confusion, respiratory depression, myoclonic jerks and pinpoint pupils), seizures (tramadol), but there is no
dose ceiling in patients who accumulate tolerance.
[citation needed]

Opioids, while very effective analgesics, may have some unpleasant side-effects. Patients starting morphine
may experience nausea and vomiting (generally relieved by a short course of antiemetics such
as phenergan). Pruritus (itching) may require switching to a different opioid. Constipationoccurs in almost all
patients on opioids, and laxatives (lactulose, macrogol-containing or co-danthramer) are typically co-
prescribed.
[7]

When used appropriately, opioids and similar narcotic analgesics are otherwise safe and effective, however
risks such as addiction and the body becoming used to the drug (tolerance) can occur. The effect of tolerance
means that frequent use of the drug may result in its diminished effect so, when safe to do so, the dosage may
need to be increased to maintain effectiveness. This may be of particular concern regarding patients suffering
with chronic pain.
[citation needed]

[edit]Iupirtine
Flupirtine is a centrally acting K+ channel opener with weak NDA antagonist properties.
[8]
t is used in Europe
for moderate to strong pain and migraine and its muscle relaxant properties. t has no anticholinergic properties
and is believed be devoid of any activity on dopamine, serotonin or histamine receptors. t is not addictive and
tolerance usually does not develop.
[9]
However, tolerance may develop in single cases.
[10]

[edit]Specific agents
n patients with chronic or neuropathic pain, various other substances may have analgesic properties. Tricyclic
antidepressants, especially amitriptyline, have been shown to improve pain in what appears to be a central
manner.
[citation needed]
Nefopam is used in Europe for pain relief with concurrent opioids. The exact mechanism
of carbamazepine, gabapentin and pregabalin is similarly unclear, but these anticonvulsants are used to treat
neuropathic pain with differing degrees of success. Anticonvulsants are most commonly used for neuropathic
pain as their mechanism of action tends to inhibit pain sensation.
[citation needed]

[edit]Specific forms and uses
[edit]ombinations
Analgesics are frequently used in combination, such as the paracetamol and codeine preparations found in
many non-prescription pain relievers. They can also be found in combination with vasoconstrictor drugs such
as pseudoephedrine for sinus-related preparations, or with antihistamine drugs for allergy sufferers.
While the use of paracetamol, aspirin, ibuprofen, naproxen and other NSADS concurrently with weak to mid-
range opiates (up to about the hydrocodone level) has been said to show beneficial synergistic effects by
combatting pain at multiple sites of action,
[11]
several combination analgesic products have been shown to have
few efficacy benefits when compared to similar doses of their individual components. oreover, these
combination analgesics can often result in significant adverse events, including accidental overdoses, most
often due to confusion which arises from the multiple (and often non-acting) components of these
combinations.
[12]

[edit]TopicaI or systemic
Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be
treated with an ibuprofen- or diclofenac-containing gel; capsaicin also is used topically. Lidocaine,
an anesthetic, and steroids may be injected into painful joints for longer-term pain relief. Lidocaine is also used
for painful mouth sores and to numb areas for dental work and minor medical procedures.
[edit]!sychotropic agents
Tetrahydrocannabinol (THC) and some other cannabinoids, either from the Cannabis sativa plant or synthetic,
have analgesic properties, although the use of cannabis derivatives is currently illegal in many countries. A
recent study finds that inhaled cannabis is effective in alleviating neuropathy and pain resulting from e.g. spinal
injury and multiple sclerosis.
[13]
Other psychotropic analgesic agents include ketamine (an NDA receptor
antagonist), clonidine and other d
2
-adrenoreceptor agonists, and mexiletine and other local anaesthetic
analogues.
[edit]AtypicaI and/or adjuvant anaIgesics
Orphenadrine, cyclobenzaprine, scopolamine, atropine, gabapentin, first-generation antidepressants and other
drugs possessing anticholinergic and/or antispasmodic properties are used in many cases along with
analgesics to potentiate centrally acting analgesics such as opioids when used against pain especially of
neuropathic origin and to modulate the effects of many other types of analgesics by action in
the parasympathetic nervous system. Dextromethorphan has been noted to slow the development of tolerance
to opioids and exert additional analgesia by acting upon the NDAreceptors; some analgesics such
as methadone and ketobemidone and perhaps piritramide have intrinsic NDA action. High-alcohol liquor has
been used in the past as an agent for dulling pain, due to the CNS depressant effects of ethyl alcohol, a
notable example being the American Civil War. However, the ability of alcohol to relieve severe pain is likely
inferior to many analgesics used today (e.g. morphine, codeine). As such, the idea of alcohol for analgesia is
generally considered a primitive practice in virtually all industrialized countries today.
The use of adjuvant analgesics is an important and growing part of the pain-control field and new discoveries
are made practically every year. any of these drugs combat the side effects of opioid analgesics, an added
bonus. For example, antihistamines including orphenadrine combat the release of histamine caused by many
opioids, methylphenidate, caffeine, ephedrine, dextroamphetamine, and cocaine work against heavy sedation
and may elevate mood in distressed patients as do the antidepressants. The use of
medicinal cannabis remains a debated issue.

ANALGESIC CLASSIFICATION

7: Class Cha7acte7stcs Examples Comments
Opo/s` Acts on pain receptors in
both spinal cord and
brain; May be used with
tranquilizers to induce a
state oI potent sedation
(neuroleptanalgesia)
Morphine Stimulates vomiting and vagal CNS
centers; Can cause excitement in cats,
horses and Iood animals; 4-6 hours
duration; May be given SC or IM to help
prevent hypotension; For moderate to
severe pain
Oxymorphone Greater analgesic and sedative eIIects
than morphine; Does not cause
hypotension; May cause excitement in
cats; May be given IV, SC, IM, or
epidurally; Approximate 4 hour
duration; For moderate to severe pain
Meperidine
(Demerol)
Rapid IV injection may cause severe
hypotension, excitement and seizures;
PainIul iI given IM; PreIerred
administration is SC; Used in dogs, cats,
and rodents; A synthetic opioid; not as
potent as above drugs; OIten used with
NSAIDs or as a preanesthetic; For mild
to moderate pain
Fentanyl One oI the most potent analgesics; Rapid
onset-short duration (IV injection 30
minutes); Usually administered by
continuous IV drip or transdermal patch;
Can cause panting and increased
sensitivity to sound; For severe to
moderate pain
Butorphanol
(Torbutrol)
Synthetic opioid- has both agonist and
antagonist properties; EIIective and saIe
post-op analgesic Ior mild to moderate
pain, especially cranial visceral;
Extensively used in dogs, cats, and
horses; May be used to help reverse
eIIects oI other opioids (respiratory
depression and sedation), while still
maintaining some analgesia; Do not give
epidurallypotentially toxic to the spinal
cord
Buprenorphine A partial agonist; Has a bell shaped
response curve (may be less eIIective at
higher doses than at moderate doses);
Delayed onset, but gives 6-12 hours
analgesia(IM) and 18-24 hours when
given epidurally; Not adequate Ior
severe pain (i.e. orthopedic pain), but is
useIul Ior mild to moderate pain;
Commonly used Ior rodents and other
species in research; Has been known to
cause pica in rats
Alpha-2
aonstsThazne
/e7;at;es
ProIound sedative eIIect;
Rapid onset; Reliable,
reversible; Good muscle
relaxation; May cause
cardiovascular side
eIIects; Use only in
healthy animals; Not Ior
very young or very old;
Use caution when
handling-may be
absorbed through skin
abrasions; Causes
transient hypoglycemia
Xylazine May be used alone or in combination
with other agents (i.e. Ketamine,
opioids) IM or IV; Will allow greatly
reduced doses oI other agents including
inhalants; May cause vomiting and bloat
(in ruminants); Can be reversed with
Yohimbine (IV)
Meditomidine
(Domitor)
Commonly used in combination with
other agents (dose oI general anesthetic
should be reduced); Less likely to cause
vomiting; May be reversed with
Atipamesole (Antesedan) which will not
reverse the eIIects oI other drugs given
concurrently with Meditomidine; *High
doses oI Atipamesole can cause panting,
excitement, muscle tremors,
hypotension, and tachycardia-especially
iI given IV
NSAI (Non-
ste7o/al ant-
nflammato7
/7:s)
Analgesic, antipyretic,
and anti-inIlammatory;
EIIective Ior
musculoskeletal pain;
Requires 30-60 minutes
Ior Iull analgesic
properties to take eIIect;
Metabolized in the liver;
Negligible eIIect on
cardiovascular and
respiratory systems
Aspirin May cause gastric irritation and
prolonged bleeding time; Prolonged halI
liIe in cats, geriatrics and neonates
Acetaminophen Toxic to cats and hepatotoxic to dogs;
Less gastric irritation than Aspirin
IbuproIen Renal, gastric eIIects; Narrow saIety
margin in cats
Flunixin
(Banamine)
SigniIicant renal toxicity is possible in
hypotensive patients; Do not use with
MethoxyIlurane
KetoproIen Potent analgesic, especially Ior
orthopedic patients; Gastric irritation
and ulceration may occur at therapeutic
doses
CarproIen
(Rimadyl)
Less potential Ior gastric ulceration than
some NSAID`s; Renal toxicity seen in
dogs with prolonged use (especially
Labrador Retrievers)
Meloxicam Can cause vomiting and diarrhea; Less
potential Ior gastric ulceration than some
NSAID`s; 5-day limit Ior treatment oI
cats
Local Analesa Can be sprayed, injected
at surgical site, or
inIiltrated around a nerve
supplying the aIIected
area; May be used to
desensitize an entire area
by using an epidural
injection
Lidocaine
(Xylocaine)
Immediate onset; Lasts about 1-2 hours
(with epinephrine) or 1 hour without
Bupivicaine Onset 20 min; Duration 4-6 hours
Mepivicaine Immediate onset; Duration 90-180
minutes
Novocaine Topical (mucous membranes) and
injectable Iorms; Immediate onset;
Duration 1 hour
Ophthane For ophthalmic use
* Must be handled in accordance with the Control Drug Act
Updated 5/21/07